Our recent studies have shown that some tripeptides are absorbed by the peptide carrier system in human intestine. There are indications that this route of transport can be of benefit to patients with digestive and absorptive disorders who normally do poorly on amino acid or whole protein diet. The purpose of the studies proposed in Part 1 of this application is to investigate the feasibility of a tripeptide diet for oral feeding in such patients. A series of experiments is proposed that will determine the composition of a tripeptide diet which will allow enhanced absorption without unfavorably affecting gastrointestinal motility, gastric and pancreatic secretion, histology and function of the intestinal mucosa, and gut flora. The effect of this diet on parameters of protein nutrition will be examined in patients with exocrine pancreatic deficiencies and short bowel syndrome. Our studies in rats have shown that dipeptides, when administered intravenously, are cleared rapidly from plasma with concomitant enrichment of the tissue pools of free amino acids and with very little loss of dipeptides in the urine. Experiments proposed in Part 2 of this application will investigate the capacity of liver, muscle and kidney to transport and hydrolyze tripeptides in rats. If these tissues are capable of efficient assimilation of tripeptides, the usefulness of tripeptides as a substrate for parenteral nutrition will be investigated by chronic infusion studies in baboons. A series of experiments is planned to compare the effect of intravenous tripeptides versus intravenous amino acids on tissue amino acid pools, protein synthesis, amino acid oxidation and hormonal secretion. These results will be used ultimately to design a tripeptide solution for intravenous use in patients in need of maintenance and improvement of their protein nutrition.